2'-Deoxycoformycin (2'-dCF), a purine nucleoside analogue produced by the microorganism Streptomyces antibioticus, is the most potent inhibitor of mammalian adenosine deaminase yet described. In man, dog and monkey, 2'dCF exhibits a potent antilymphocytic effect. This effect appears to result from intracellular accumulation of 2'-deoxyATP, as a consequence of the block by 2'-dCF of the normal catabolic deamination route for endogenous adenosine and 2'-deoxyadenosine. In support of an ongoing Phase I study of 2'-dCF at the Royal Marsden Hospital, this laboratory has carried out extensive study of the clinical pharmacology of the drug. 2'dCF levels were determined in plasma and urine samples received from eighteen patients: the rate of total body clearance of the drug was significantly slower than that observed in previous studies in the dog. In man, 2'dCF showed specific toxicity toward leukemic lymphoblasts: this effect could not be demonstrated in murine leukemia tumor models, however, unless the drug were supplemented with exogenous 2'-deoxyadenosine.